Fluid and Electrolyte balance Dr Sanjay De Bakshi MS;FRCS Distribution of body water DISTRIBUTION TOTAL BODY WATER 60% PLASMA 5% INTERSTITIAL FLUID 15% INTRACELLULAR WATER 40% Distribution of Body Water (contd.) tF Ad ul tM Ad ul s ant inf s neo nat e • Neonates---75 to 80%. • Infants.
Download ReportTranscript Fluid and Electrolyte balance Dr Sanjay De Bakshi MS;FRCS Distribution of body water DISTRIBUTION TOTAL BODY WATER 60% PLASMA 5% INTERSTITIAL FLUID 15% INTRACELLULAR WATER 40% Distribution of Body Water (contd.) tF Ad ul tM Ad ul s ant inf s neo nat e • Neonates---75 to 80%. • Infants.
Slide 1
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 2
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 3
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 4
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 5
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 6
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 7
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 8
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 9
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 10
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 11
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 12
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 13
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 14
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 15
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 16
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 17
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 18
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 19
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 20
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 21
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 22
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 23
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 24
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 25
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 26
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 27
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 28
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 29
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 30
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 31
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 32
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 33
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 34
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 35
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 36
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 37
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 38
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 39
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 40
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 41
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 42
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 43
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 44
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 45
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 46
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 47
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 48
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 49
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 50
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 51
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 52
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 53
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 54
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 55
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 56
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 57
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 58
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 59
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 60
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 61
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 62
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 63
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 64
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 65
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 66
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 67
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 68
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 69
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 70
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 71
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 72
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 73
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 74
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 75
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 76
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 77
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 78
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 79
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 80
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 81
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 82
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 83
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 84
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 85
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 86
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 87
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 88
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 89
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 90
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 91
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 92
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 93
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 94
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 95
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 96
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 97
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 98
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 99
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 100
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 101
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 102
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 103
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 104
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 105
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 106
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 107
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 108
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 109
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 110
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 111
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 112
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 113
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 114
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 115
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 116
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 117
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 118
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 119
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 120
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 121
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 122
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 123
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 124
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 125
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 126
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 127
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 128
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 129
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 130
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 131
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 132
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 133
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 134
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 135
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 136
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 137
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 138
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 139
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 2
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 3
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 4
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 5
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 6
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 7
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 8
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 9
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 10
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 11
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 12
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 13
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 14
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 15
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 16
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 17
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 18
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 19
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 20
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 21
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 22
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 23
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 24
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 25
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 26
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 27
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 28
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 29
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 30
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 31
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 32
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 33
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 34
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 35
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 36
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 37
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 38
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 39
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 40
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 41
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 42
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 43
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 44
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 45
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 46
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 47
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 48
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 49
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 50
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 51
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 52
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 53
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 54
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 55
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 56
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 57
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 58
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 59
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 60
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 61
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 62
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 63
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 64
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 65
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 66
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 67
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 68
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 69
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 70
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 71
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 72
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 73
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 74
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 75
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 76
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 77
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 78
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 79
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 80
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 81
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 82
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 83
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 84
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 85
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 86
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 87
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 88
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 89
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 90
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 91
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 92
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 93
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 94
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 95
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 96
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 97
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 98
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 99
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 100
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 101
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 102
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 103
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 104
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 105
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 106
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 107
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 108
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 109
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 110
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 111
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 112
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 113
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 114
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 115
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 116
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 117
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 118
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 119
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 120
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 121
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 122
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 123
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 124
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 125
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 126
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 127
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 128
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 129
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 130
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 131
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 132
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 133
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 134
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 135
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 136
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 137
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 138
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!
Slide 139
Fluid and Electrolyte
balance
Dr Sanjay De Bakshi
MS;FRCS
Distribution of body water
DISTRIBUTION
TOTAL BODY WATER
60%
PLASMA
5%
INTERSTITIAL FLUID
15%
INTRACELLULAR WATER
40%
Distribution of Body Water (contd.)
tF
Ad
ul
tM
Ad
ul
s
ant
inf
s
neo
nat
e
• Neonates---75 to
80%.
• Infants and
children------65%.
• Adults:Males----60%
Females---50%.
80
70
60
50
40
30
20
10
0
Distribution of Body Water (contd.)
Body water is also
inversely proportional to
body fat.
Measurement of Body water and
its Components
TOTAL BODY WATER
(60%)
INTRACELLULAR
FLUID
(40%)
EXTRACELLULAR
FLUID
(20%)
Tracer-thiosulphate
PLASMA
(5%)
(Radio-iodinated Almumin)
INTERSTITIAL
FLUID (15%)
(ECF-Plasma)
WATER EXCHANGE
WATER EXCHANGE
(60 to 80kg man.)
GAIN
Avg. daily
vol.(mL)
Minimal
mL
Maximal
mL
Sensible
Oral fluids
800-1500
0
1500/hr.
Sensible
Solid foods
500-700
0
1500
Insensible
Water of oxidation
250
125
800
Insensible
Water of solution
0
0
500
Routes of H2O gain
WATER EXCHANGE
LOSS
H2O loss
Routes
Average
daily
Vol, mL
Minimal
mL
Maximal mL
Sensible
Urine
Sensible
Intestinal
Sensible
Sweat
Insensible
Lungs
Insensible
Skin
800-1500
300
0-250
0
1400/h in
Diabetes In
2500/h
0-250
0
2400/h
250
125
800
600
600
1500
MRI OF THE
BRAIN
SAGGITAL
SECTION
Center for Water Balance
Flow of CSF
• Lateral ventricles
– Interventricular
foramen (Monro)
• 3rd ventricle
– Cerebral aqueduct
(Sylvius)
• 4th ventricle
– Central canal of spinal
cord (Magendie and
Luschka)
– Subarachnoid space
• Around brain
• Around spinal cord
Function of Cerebrospinal Fluid
• Cushions and supports brain
• Transports respiratory gases, nutrients,
wastes
– Ependymal cells
• Produced by the choroid plexus
– Network of capillaries in each ventricle
– Materials for CSF taken from blood
– Replaced every 8 hours
• Via projections from the subarachnoid space into
the dural sinuses
• Removed during a spinal tap for diagnosis
of meninges or brain infections
Control of Water Intake
In humans, the thirst center is located in the anterior
hypothalamus. The primary stimuli for thirst are
hypertonicity and hypovolemia.
Osmoreceptors in the anterior wall of the third ventricle
mediate the osmotic regulation of thirst.
Hypovolemia and hypotension stimulate thirst through the
activation of low-pressure (venous) and high-pressure
(arterial) vascular stretch receptors. Impulses from these
receptors are transmitted by the vagus and the
glossopharyngeal nerves to the medulla and from there to
the hypothalamus.
In addition, the hypothalamus is stimulated directly by
angiotensin II.
The hypothalamus and thirst
response
THIRST CENTER STIMULATED
BY:1) Increased Plasma Osmolarity
Increased thirst
Increased ADH
2) Decreased ECF Volume
a) Decreased stimulation of
Atrial Type B receptors
Increased sympathetic stimulation
b) Decreased pressure at Renal Afferent Arteriole
Stimulation of Angiotensin mechanism
c) Low Sodium causes stimulation of the Renin-angiotensin
System
Increased Angiotensin II
Vasoconstriction
ADH
Aldosterone
Thirst
Renin angiotensin
mechanism
Low pressure at the
afferent arteriole.
Low sodium at the
macula densa
Increased Renin sectretion
from the JG apparatus
JG cells, Macula densa & Lacis
(Polkissen)cells
AngiotensinI
ACE
Angiotensin
Angiotensin II
Fluid exchange
Fluid dynamics at the capillary
CHP = Capillary
Hydrostatic
Pressure
COP = Capillary
Osmotic Pressure
IFHP = Interstitial
Fluid Hydrostatic
Pressure
IFOP =Interstitial
Fluid Osmotic
Pressure
Osmotic pressure
• DEFINITION:- Is the pressure that drives
water across the semipermeable cell
membrane and is dependant on those
substances which fail to pass through the
membrane.
• The total number of osmotically active
particles is approximately 290 to 310 mO
in each component.
Some more definitions
What is a Mole and a Molar Solution?
• Molarity- A mole is a gram molecular
weight of a substance.
NaCl=58.5gm; C6H12O6=180gm.
• 1 molar solution = gram molecular
weight of the substance in a litre of
solution. 1 mol= 1000mmol.
Some calculations
• OSMOTIC PRESSURE depends on the actual
number of particles in solution.
• Therefore,
1 gram mol weight of NaCl ie. 58.5gm of NaCl in
1 litre exerts how much of osmotic pressure?
58.5gm NaCl exerts--------------2000mosmol/L
9gm NaCl exerts--------------2000 x 9
58.5
= 307.69 mosmol/L
180gm C6H12O6 exerts------------1000mosmol/L
50gm C6H12O6 exerts-----------1000 x 50
180
= 277.77 mosmol/L
IONIC COMPOSITION OF
DIFFERENT BODY FLUIDS
INTRACELLULAR
CATIONS
Na = 10
K = 150
Mg = 40
ANIONS
HPO4 =
150
SO4 =
150
HCO3 =
10
Prt = 40
PLASMA
ECF
CATIONS
ANIONS
CATIONS
ANIONS
Na = 142
Cl = 103
Na = 144
Cl = 114
K = 4
K = 4
Ca = 5
HCO3 =
27
SO4 = 3
Ca = 3
HCO3 =
30
SO4 = 3
Mg = 3
PO4 = 3
Mg = 2
PO4 = 3
Urea = 24
Org Ac =
5
Org Ac =
5
Prt = 16
Prt = 1
OSMOLAR GAP
The osmolality gap is an indication of unmeasured solute in the
blood.This is caused because complete dissociation of particles
in vivo is only 93%.
It is determined by the measured osmolality (MO) minus the
calculated osmolality (CO).
• CO = 2 X [Na]+[glucose (mg/dl)] / 20 + [urea (mg/dl) ] / 3 - 2
A large positive (>14) osmolality gap can help identify
the presence in plasma of substances such as ethanol,
methanol, isopropanol, ethylene glycol, propylene
glycol, and acetone.
ANION GAP
• Proper interpretation of the OG also requires
knowledge of the anion gap (AG = Na - HCO3 - Cl),
the blood pH, and qualitative testing of the plasma
ketone bodies (KETO). Determinations of MO and
for CO should be performed on the same plasma
sample.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
Importance of Osmolar and Anion Gap
• When the OG is combined with blood pH and AG,
poisonings with toxic alcohols can be quickly recognized.
The presence of low blood pH, elevated AG, and greatly
elevated OG (>14) is a medical emergency that requires
prompt treatment.
SITUATION
pH
AG
KETO
GLU
OG
(mOsm/kg H20)*
Ethanol only
N
N
N
N
HI
100 mg/dl = 21.7
LO
HI
N
N or HI
N or HI**
50 mg/dl = 15.6
N
N
POS
N
HI
100 mg/dl = 16.7
(also acetone)
Ethylene Glycol
LO
HI
N
N
HI
50 mg/dl = 8.1
Alcoholic Ketoacidosis
LO
HI
Weak
POS
300
HI
(ethanol)
Diabetic Ketoacidosis
LO
HI
POS
300
N or UP
(usually < 20-25)
50 mg/dl = 8.6
(acetone)
Methanol (late)
Isopropanol
Case Study:
• A sixty-seven year old white male was
found pulseless and resuscitated; then
brought to the emergency room. He
had been reported to be drinking in a
bar all afternoon, and had then fallen
from a ten foot balcony to snow
covered ground. He arrived in the
emergency room with a fractured
occiput and was unresponsive.
Admission Data:
Na=141 mEq/l
Urea=8 mg/dl
pH=7.30
Cl=105 mEq/l
GLU=181 mg/dl
MO=353 mOsm/kg
HCO3=19 mEq/l
KETO=Neg
Anion Gap = Na - Cl- HCO3= 141 - 105- 19 = 17
Calculated Osmolality =
2 x Na + GLU/20 + Urea/3 -2 = 282+ 181/20 + 8/3 -2 = 292
0smolar Gap = MO - CO= 353 - 292 = 61
If we assume OG is due to ethanol, then ethanol concentration would
be 61/21.7 x 100 mg/dl = 281 mg/dl
The measured ethanol concentration on this sample was 270 mg/dl.
What are
aquaporines?
Water
Aquaporine are proteins,
which form a water-leading
channel by the cell wall; it is
situated in the otherwise
impermeable cell membrane
of many plants and animals.
Although these filters are
very fine pored, Aquaporine
achieve an amazingly high
water conductivity of up to
three billion water molecules
per second per channel.
A 10x10 cm 2 large diaphragm
with embedded Aquaporines
could filter about a litre
water in approximately
--7 seconds.
Figure: The AQP1 tetramer
viewed looking down the pores
from the cytoplasmic side, normal
to the membrane. One monomer
of the four is represented as a
solid space-filling model.
The overall structure of AQP1 is
that of a tetramer, the four
parts (monomers) of which
each define a single pore.
These monomers are arranged
side by side in a tight cluster, with
the pores running parallel. Each
monomer in turn comprises six
membrane-spanning helices that
partially surround two shorter
helices. The short non-membranespanning helices make up the
major portion of the pore. Each
pore has a dumbbell-like shape.
One broad end is the cytoplasmic
vestibule; the other is the
extracellular vestibule. The bar of
the dumbbell is the selectivity
filter, which narrows to a
constriction region on the
extracellular end.
Computer simulation of the action of Aquaporines
Left: Water molecules (red/white) diffuse over Aquaporin (blue)
by the cell membrane (yellow/green).
The cutout right shows the ' dance ' of an individual water
molecule on its way by the channel."
“Diagram: Max-Planck-Institut for Biophysical Chemistry "
Case Study :
CAUSE:Infused 5% Dextrose
only on Day 1.
Plenty of plain water
orally on Day 2.
A healthy young lady of 32yrs.
Undergoes an appendicectomy.
She is fine till the third postoperative day, when she has
three grand mal seizures. She
recieves 20mgm of diazepam
and 250mgm of Phenytoin IV
and undergoes laryngeal
intubation with mechanical
ventilation.
Case Study :
Withhold water.
Infusion of 3 per cent
Sodium Chloride.
Intravenous
administration of
20mgm of
Furosemide.
• Her body weight is 46kgs.
• Sodium concentration112mmol/litre
• Potassium concentration4.1 mmol/litre
• Serum osmolality228mOsm/kg of water.
• Urine osmolality510mOsm/kg of water.
TYPES OF HYPONATRAEMIA
TYPES OF
HYPONATRAEMIA
Euvolemic
hyponatremia
TBW increases
while total
sodium remains
normal. The
ECF volume is
increased
minimally to
moderately, but
edema is not
present
Hypervolemic
hyponatremia
Total body sodium
increases, and
TBW increases to
a greater extent.
The ECF is
increased
markedly, and
edema is present.
Hypovolemic
hyponatremia
Total body water
(TBW) decreases;
total body sodium
(Na+) decreases
to a greater
extent. The
extracellular
fluid (ECF) volume
is decreased.
Redistributive
hyponatremia
Water shifts from
the intracellular to
the extracellular
compartment,
with a resultant
dilution of sodium.
The TBW and
total body sodium
are unchanged.
This condition
occurs with
hyperglycemia
Pseudohyponatremia
The aqueous
phase is diluted
by excessive
proteins or lipids.
The TBW and
total body
sodium are
unchanged. This
condition is seen
with
hypertriglyceride
mia and multiple
myeloma.
Pathophysiology: Serum sodium is
regulated by
thirst,
ADH,
the renin-angiotensin-aldosterone
system, and
variations in renal handling of
K+
filtered sodium.
Increases in serum osmolarity above Vol
the normal range (280-300
mOsm/kg) stimulate hypothalamic
osmoreceptors, which, in turn,
cause an increase in thirst and in
circulating levels of ADH.
ADH
Free water
absorption
from the
Kidneys
Aldosterone
Absorption of
sodium at the
distal renal
tubule.
NORMAL SODIUM BALANCE
INTAKE 80 –100 mmols/day (5-6gms)
Secretions
1000mmols/day
Plasma Sodium
(136-144mmols)
PCT
75%
GI TRACT
Faeces 5mmols/day
Kidney
LH
22%
DCT
4-5%
CD
2-3%
Loss in Urine (70-90mmols/day)
Clinical features of hyponatraemia
•
•
•
•
•
•
•
•
Anorexia
Nausea and vomiting
Difficulty concentrating
Confusion
Lethargy
Agitation
Headache
Seizures
Hypovolemic hyponatremia sodium and free water are lost and
replaced by inappropriately
hypotonic fluids, such as tap
water, half-normal saline, or
dextrose in water
o Excess fluid losses (eg, vomiting,
diarrhea, excessive sweating, GI fistulas
or drainage tubes, pancreatitis, burns)
that have been replaced primarily by
hypotonic fluids
o Acute or chronic renal insufficiency
o Salt-wasting nephropathy
o Cerebral salt-wasting syndrome
H2O
Na
H2O
Euvolemic hyponatremia
implies normal sodium stores H2O
and a total body excess of
free water. This occurs in
patients who take in excess
fluids.
o Psychogenic polydipsia, often in
psychiatric patients
o Administration of hypotonic
intravenous (IV) or irrigation fluids in
the immediate postoperative period
o Infants who may have been given
inappropriate amounts of free water
Na
Hypervolemic hyponatremia
occurs when sodium stores
increase inappropriately.
o History of hepatic cirrhosis,
congestive heart failure, or
nephrotic syndrome, in which
patients are subject to insidious
increases in total body sodium
and free water stores
o Uncorrected hypothyroidism or
cortisol deficiency
o SIADH
o Consumption of large quantities
of beer or use of the recreational
drug MDMA (ecstasy)
Na
H2O
HYPONATRAEMIA
Plasma osmolality
High
Normal
Low
Hyperglycaemia
Mannitol
Hyperproteinaemia
Hyperlipidaemia
Maximal volume of
maximally dilute urine
No
Yes
ECF volume
Primary polydipsia
Reset osmostat
Increased
Increased
Decreased
Heart failure
Hepatic cirrhosis
Nephrotic syndrome
Renal insufficiency
SIADH
Hypothyroidism
Adrenal insufficiency
Urine sodium
Concentration
<10mmol/l
>20 mmol/l
External Na loss
Remote diuretic use
Remote vomiting
Na+ wasting nephropathy
Hypoaldesteronism
Diuretic
Vomiting
GI or Skin
Effect of hyponatraemia
and its correction
Water
gain
Normal
Immediate
effect of
hypo state
Osmotic
demyeli
nation
Proper
therapy
Incorrect
therapy
Loss of
Water
organic
osmolytes
Slow
adaptation
Rapid
adaptation
Loss of
Na, K, Cl.
Treatment of Hyponatraemia
In asymptomatic patients: When symptoms are absent, the
focus of therapy should be on identifying and correcting the
underlying cause of hyponatraemia.
If hypovolemic on the basis of clinical assessment and urine
sodium concentration, normal saline solution should be
administered initially to correct the extracellular fluid
volume deficit.
If hypervolemic, salt and water restriction is key.
If euvolemic and hyponatremic, therapy consists primarily
of water restriction. When the cause of the syndrome of
inappropriate ADH is unknown or not treatable, other
methods can be used, including increased dietary protein and
salt and use of urea, loop diuretics and, rarely,
demeclocycline hydrochloride (Declomycin).
Treatment of Hyponatraemia
In symptomatic patients: Patients with acute symptomatic
hyponatremia are candidates for aggressive treatment
Hyponatremia can be corrected with administration of
hypertonic saline solution (3%) at a rate of about 1 mL/kg
per hour. A loop diuretic may be added to enhance water
excretion if urine osmolality is greater than 300 mOsm/kg.
The serum sodium concentration should be raised no more
than 25 mEq/L in the first 48 hours, at a rate of no more
than 2 mEq/L per hour, and the target goal should be 120 to
125 mEq/L.
With use of this combination therapy, sodium lost in the urine
is replaced with an equal amount of sodium in a smaller
volume.
Treatment with hypertonic saline solution is advocated only for
patients with severe hyponatremia who have profound
neurologic symptoms.
Case Study :
1
• An elderly lady of 63yrs. Undergoes a difficult
resection- anastomosis for a gangrenous segment
of small intestine, which was incarcerated under
a post-operative band.
• Her abdomen is distended, she is obtunded, and
her bowel sounds are absent.
• The tongue is red and swollen, skin turgor is
diminished and she is not totally coherent.
• She has mild orthostatic hypotension
Case Study :
Straight X-ray
CT Scan
• Serum sodium158mmol/liter
• Serum Potassium4.0mmol/liter
• Body weight is
60kg.
TYPES OF
HYPERNATRAEMIA
In general, hypernatremia is due to too little water, too
much salt, or a combination thereof.
HYPERNATRAEMIA
Hypovolemic hypernatremia Hypervolemic hypernatremia Euvolemic hypernatremia
water deficit >sodium deficit sodium gains >water gains sodium gains =water gains
H2O
Na
Na
H2O
Na
H2O
HYPERNATRAEMIA
urine electrolytes .
(sodium, osmolality, and, possibly, potassium and creatinine)
serum glucose
urine osmolarity
is high
urine osmolality
Isotonic
extrarenal hypotonic fluid losses
diuretics,
vomiting, low sodium diarrhea, sweat,
evaporation from burns, low sodium ostomy output
osmotic diuresis (mannitol, glucose, urea)
or salt wasting.
urine osmolality
is low
Diabetes Insipidus
salt overload states
total volume should increase
THUMB RULE:•Serum sodium levels of more than 190 mEq/L usually indicate
long-term salt ingestion.
•Serum sodium levels of more than 170 mEq/L usually indicate DI.
•Serum sodium levels of more than 150-170 mEq/L usually
indicate dehydration.
Hypovolemic hypernatremia (ie, water
deficit >sodium deficit)
• Extrarenal losses - Diarrhea, vomiting,
fistulas, significant burns
• Renal losses - Osmotic diuretics,
diuretics, postobstructive diuresis,
intrinsic renal disease
• Adipsic hypernatremia is secondary to
decreased thirst. This can be
behavioral or, rarely, secondary to
damage to the hypothalamic thirst
centers.
H2O
Na
Hypervolemic hypernatremia
(ie, sodium gains >water
gains)
• Hypertonic saline
• Sodium bicarbonate
administration
• Accidental salt ingestion
• Mineralocorticoid excess
(Cushing syndrome)
H2O
Na
Euvolemic hypernatremia
• Extrarenal losses - Increased
insensible loss (eg, hyperventilation)
• Renal losses - Central DI,
nephrogenic DI
These patients appear euvolemic
because most of the free water loss
is from intracellular and interstitial
spaces, with less than 10%
occurring from intravascular space.
Typically, symptoms result if serum
sodium is more than 160-170
mEq/L.
H2O
Na
Effect of Hypernatraemia
and its correction
Normal
brain
Waterloss
Hypertonic
state
Rapid
adaptation
CEREBRAL
OEDEMA
Acc. Of
organic
CORRECTIONosmolytes
PROPER
IMPROPER
CORRECTION
Water
Slow
adaptation
Acc. of
electrolytes
Treatment of Hypernatraemia
Treatment
Same general principles as that of hyponatremia .
Rapid correction should be avoided because of the
brain's adaptive response to hypernatremia and
the potential risk of cerebral edema.
The current recommendation is to lower the
serum sodium concentration by about 0.5 mEq/L
per hour and to replace no more than half the
water deficit in the first 24 hours.
The following formula can be used to calculate the
water deficit (total body water, in kilograms, is
60% of lean body mass in men and 50% in women):
Water deficit = total body water (serum sodium
concentration ÷ 140 - 1)
Treatment of Hypernatraemia
In hypovolemic hypernatremia, normal
saline solution is indicated initially to
correct the intravascular volume deficit.
When that is accomplished, more hypotonic
fluids (eg, 50% normal saline) can be used.
In hypervolemic hypernatremia, removing
the source of salt excess, administering
diuretics, and replacing water are
important to successful therapy.
In euvolemic hypernatremia usually require
water replacement alone--either free
water orally or an infusion of 5% dextrose
in water.
Case Study :
2
A 70 yr old poorly controlled
diabetic lady presented with
features of peritonitis. A straight
X -ray showed the following. The
1st post-operative day found her
delirious, oliguric, with a feeble
thready pulse and low blood
pressure.She started to retain
CO2 and needed to be put on
ventilation.
Case Study :
BLOOD RESULTS
TREATMENT:1)Large amounts of fluids
to rapidly establish circ.
And urinary flow.
2)Insulin for rapid corretion
of hyperglycaemia.
3)Potassium to replenish
intracellular shifts.
•
•
•
•
•
•
Blood Sugar -768mgm%.
Serum Potassium-4.5mmol/L
Serum Sodium- 138mmol/L
Serum Creatinine-1.8ugm/dl
Serum Osmolality-360mmol/L
Urine-no ketone bodies
MICROSCOPIC ANATOMY OF THE NEPHRON
FUNCTION OF THE KIDNEY
-and the action of diuretics.
CORTEX
•
•
Na;Cl;
NaHCO3
H2O
Na
Na;Cl
K;H
Na
H2O
•
•
MEDULLA
H2O
Na;Cl
1) Proximal tubule-osmotic
diuresis.
2) Ascending limb of the
loop of Henle-reduction of
Na reabsorption(K loss at 4).
3) Cortical diluting segmentreduction of Na
reabsorption(K loss at 4).
4) Distal tubule-inhibition of
Na exchange with K,Haldosterone
antagonism/independent.
Site of Action of Diuretics
• 1) Proximal tubule and
descending limb of the
Loop of Henle-osmotic
diuresis.
• 2) Proximal tubule –
Carbonic anhydrase
inhibitors
• 3) Thick ascending limb
of the loop of Henleloop diuretics
• 4) Distal tubulethiazide diuretics and
potassium-sparing
diuretics.
Case Study:
• A 62 year old man, presents with
painless,profuse projectile
vomiting containing old food
material
• No history of any previous
surgery, he complains of a long
standing, mild
• Epigastric pain.
• On Examination; the patient had a
BP of 100/60;Pulse110/min.Eyes
shrunken,
• Decreased skin turgor, slow to
questions, decreased tendon
reflexes, a scaphoid abdomen with
a visible peristalsis moving from
left to right, no free fluid or lump in
the abdomen.
• Barium meal X-ray showed the
following
3
Case Study :
Pylorus
Upper GI Endoscopy
Revealed the
following finding.
Case Study :
Blood tests.
Na mmol/L
120
HCO3
mmol/L
36
K mmol/L
2.8
Creatinine
ugm/dl
1.3
Cl mmol/L
80
Urea
mgm/dl
62
Composition of Different Intestinal Juices
Secretions
Na
K
Cl
Saliva
Gastric
Duodenum
Ileum
Colon
Pancreas
Bile
Stool
Diarrhoea
Mixed G A
2-10
20-30 8-18
9-116
0-30
8-154
140
5
80
80-150
2-8
45-137
60
30
40
115-185
3-7
130-160
HCO3 Volume
30
0.5-2L
0-15
0.1-4L
0.1-2L
30
0.1-0.9L
55-95
115
0.1-0.8L
3-12
90-180
35
0.05-0.8L
35
70
20
30-140
30-70 73
120
10
100
20-80
Principle of Hypokalaemia
•
•
•
•
•
Direct potassium losses contribute only
minimally to actual loss.
Loss of gastric acid leads to metabolic
alkalosis which increases tubular cell
potassium concentration.
Elevated plasma bicarbonate leads to
increased bicarb to distal nephron,
leading to an augmentation of
potassium loss.
Secondary aldosteronism augments
potassium excretion
Hypokalaemia-induces the excretion of
H+ ions in place of K+ ionsPARADOXIC ACIDURIA
Case Study :
• A 32yr. old man presented with a history of severe
diarrhoea, occasionally blood stained, with a
history of rapid weight loss and severe weakness.
• His father and uncle had apparently some “bowel
problems” for which they were both operated.
• Examination showed signs of dehydration, with
diminished muscle tone and reflexes. His abdomen
was slightly distended with diminished peristaltic
sounds.
Case study -Blood results
•
•
•
•
•
•
•
Haemoglobin- 8.2mgm%
TLC- normal
Urea- 57mgm/dl
Creatinine-0.9ugm/dl
Sodium- 130mmol/L
Potassium-2.5mmol/L
Bicarbonate-13mmol/L
Case study -investigations.
FAP with diarrhea causing HYPOKALAEMIA
oVomiting or nasogastric suctioning
oRenal tubular acidosis
oDiarrhea
oHyperaldosteronism
oEnemas or laxative use
oMagnesium depletion
oLeukemia (mechanism uncertain)
oIleal loop
HYPOKALAEMIA
· Renal losses
· GI losses
· Medication effects
· Transcellular shift
oDiuretics (most common cause)
oBeta-adrenergic agonists
oSteroids
oTheophylline
oAminoglycosides
oInsulin
oAlkalosis
Malnutrition or decreased
dietary intake, parenteral
nutrition
HYPOKALAEMIA
HYPOKALAEMIA
BLOOD PRESSURE
Normal
Hypertension
Urine K+
Plasma renin
<25 mmol/l
>25mmol/l
High
Low
Serum HCO3
Serum HCO3
Malignant hypertension
Renin-secreting tumour
Plasma aldosterone
Low/Normal
High
Low
High
High
Low
GI losses
Deficient intake
Diuretics
Renal tubular
acidosis
Diabetic acidosis
Vomiting
Diuretics
Bartter's
Hyperaldosteronism
Glucocortocoid excess
Licorice
POTASSIUM
BALANCE
LOSS
ECF
ICF
10%
350mEq
90%
3150mEq
3.5-5mEq/L
URINE (90-95mEq/D)
STOOL (5-10mEq/D)
SWEAT (<5mEq/D)
140-150mEq/L
Bone 300mEq (8.6%)
Muscle 2650 mEq/L(76%)
Urine 90-95mEq/L(1%)
Liver 250mEq/L(7%)
Interstitial fluid
35mEq/L(0.4%)
RBC 250mEq/L(7%)
POTASSIUM
BALANCE
ECF
ACIDOSIS
ALKALOSIS
INSULIN
GLUCAGON
Beta-ADRENERGIC
Alpha-ADRENERGIC
ALDOSTERONE
EXERCISE
ICF
RENAL
POTASSIUM
HANDLING
10-15%
100%
50%
30%
50%
30%
140%
muscle weakness & muscle
cramping,
paralytic ileus
hypoventilation
paralysis and respiratory failure
hypotension,
tetany, and
rhabdomyolysis
cardiac effects of hypokalemia--- premature ventricular and
atrial contractions, ventricular
and atrial tachyarrhythmias, and
second or third degree
atrioventricular block.
ECG CHANGES ARE:The characteristic ECG changes of
ST segment depression, increased
U-wave amplitude, and T-wave
amplitude less than U-wave
amplitude (in the same lead)
EFFECT OF
HYPOKALAEMIA
Treatment of Hypokalaemia
If K+ is between 2.5 - 3.5 mmol/L &
no symptoms of hypokalaemia
• use oral K+ supplements, at least
80mmol/24 hours
• normal maximum daily oral dose is
100mmol/l
•may cause nausea, vomiting and GI
ulceration
•K+ must be closely monitored and
supplements stopped when K+ > 4.0 mmol/l
Treatment of Hypokalaemia
If K+ is < 2.5 mmol/l and a clinical decision is made to
treat with IV Potassium
• Use IV potassium either centrally or peripherally.
• Ready-made potassium containing infusion bags should
be prescribed and administered, unless there is a
specific indication to do otherwise
• A syringe pump may be used for central line
administration.
• All patients treated with IV potassium should have at
least once daily measurement of serum potassium until
levels are shown to be satisfactory
Treatment of Hypokalaemia
Peripheral Line IV
Administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• 40mmol/l
Phlebitis may occur at
concentrations >
30mmol/l
Central Line IV
administration
Rate of Administration
• 10mmol/hour
Maximum
20mmol/hour with ECG
monitoring
Maximum Concentration
• Can give undiluted KCL
2mmol/ml at a rate of
10-20mmol/hr via a
syringe driver with
appropriate ECG
monitoring
Caution!!
Strong Potassium Chloride Solution:
• restricted to ICU,CICU,CCU
• 10ml (20mmol) must be diluted to at least
500ml for peripheral administration
• dilute with sodium chloride 0.9%
• MIX WELL (otherwise, potassium chloride
being heavier than the usual diluents will
sink to the bottom if not mixed
sufficiently and be given in effect
undiluted as a bolus; this can be fatal)
Case Study :
4
• An 62 yrs old farmer, sustained a crush injury to both his
legs due to a tractor injury
• He was admitted at a peripheral hospital for 3 days before
being transferred to the referral center.
• On examination he was found to have a thready irregular
pulse, hypotension, was oliguric.
• The crush injury to both his legs were severe, with absent
peripheral pulses with a compound injury to the right leg
and a compartment syndrome of the left leg.
• In the past, the only relevent history was that of long
standing small joint arthritis for which the patient had been
on NSAIDS.
Case Study:
ECG
Urea-112mgm/
Creatinine-2.2ugm
Na-138mmol/l
K-7.4mmol/l
Hb-7.6mgm/dl
TLC-15600; N 86
X-Ray-bilateral
comm.# tib/fib
CAUSE: HYPERKALAEMIA(muscle damage+NSAIDS)
CAUSES OF
HYPERKALAEMIA
HYPERKALAEMIA
Excessive intake
Excessive potassium
intake alone is an
uncommon cause of
hyperkalemia
Decreased excretion
Shift from intracellular
to extracellular space
•renal failure
•rhabdomyolysis
•drugs that interfere
with potassium
excretion
•tumor lysis
•angiotensinconvening enzyme
inhibitor
•acute acidosis.
•NSAIDs
•type IV renal tubular
acidosis
•insulin deficiency
Treatment of Hyperkalaemia
Emergency treatment of hyperkalemia is targeted
towards one of three objectives:
• Antagonizing calcium, eg Calcium Chloride
administration
• Causing potassium to shift into cells, eg with
administration of sodium bicarbonate, insulin +
glucose, or nebulized albuterol
• Removing potassium from the body, eg with diuresis
with a non-potassium-sparing diuretic,
administration of cation exchange resin, or dialysis
Treatment of Hyperkalaemia
Therapy
Dose
5-10 ml IV of 10%
Calcium chloride
solution (5001000mg
Sodium bicarbonate 1 mEq/kg IV bolus
Insulin plus glucose Regular insulin 10 U
(use 1 unit of
IV plus 50 ml D50 (25
insulin/2.5 g glucose) g glucose) IV bolus
10-20 mg nebulized
Nebulized albuterol
over 15 minutes
Onset of Effect
Duration of
Effect
1-3 minutes
30-60 minutes
5-10 minutes
1-2 hours
30 minutes
4-6 hours
15 minutes
15-90 minutes
Furosemide
40-80 mg IV bolus
With onset of diuresis
Until diuretic effect
ends
Kayexalate
15-50 g PO or PR,
plus sorbitol
1-2 hours
4-6 hours
Immediate
Until dialysis
completed
Peritoneal dialysis or
Per institution
hemodialysis
Case Study
5
• A 8-year-old male child presented
with swelling neck right side since
last 2 months. There were no other
significant complaints. USG neck
showed a hypoechoic nodule of size
23x14mm in the inferior portion of
right lobe of thyroid and was highly
suspicious of neoplastic lesion.
Corroborated by the CT Scan.
• Thyroid profile was within normal
limits. FNAC of thyroid swelling
revealed to be a case of papillary
carcinoma.
• Patient was taken up for total thyroidectomy.
On exploration, it was observed that the area
surrounding the thyroid was also infiltrated
by the tumour and was unseparable from the
thyroid mass. Hence, parathyroid glands were
also removed alongwith the lymph nodes of
jugular chain.
• Histopathological examination confirmed the
diagnosis of PTC infiltrating the parathyroid
with lymph node metastasis.
WHAT ARE THE PRECAUTIONS YOU WOULD WARN
THE NURSING STAFF ABOUT AND WHAT WOULD
YOU EXPECT THEM TO LOOK FOR?
CAUSES OF HYPOCALCAEMIA
•
•
•
•
•
•
Hypoparathyroidism
Severe pancreatitis
Renal failure
Massive blood transfusion
Sepsis
Alkalosis.
CAUSES OF
HYPOCALCAEMIA
PTH
ABSENT
HYPO
PARATHYROIDISM
HERIDITARY
ACQUIRED
HYPO
MAGNESAEMIA
PTH
INEFFECTIVE
PTH
OVERWHELMED
CHRONIC RENAL
FAILURE
SEVERE ACUTE
HYPOPHOSPHATAEMIA
ACTIVE VITAMIN D
ABSENT
OSTEITIS FIBROSA AFTER
PARATHYROIDECTOMY
ACTIVE VITAMIN D
INEFFECTIVE
PSEUDO
HYPOPARATHYROIDISM
Vit D
Metabolism
Treatment of hypocalcaemia
• Airway must be secured.
• Oxygen by mask.
• ECG monitoring while treatment is
progressing.
• 10-20 ml of 10% Calcium gluconate IV
slowly. Then 40ml of 10% Calcium Gluconate
in 500 ml Saline in the next 4-8hrs.
• Oral Calcium and Vitamin D or its
metabolites
Case Study
A 38year old female executive has the following
complaints:-
6
• Loss of energy and feeling old.
• Can't concentrate and feels depressed, irritable
and has insomnia.
• Bones hurt; particularly the bones in the legs and
arms.
• Has heartburn.
• Has Recurrent Headaches and Palpitations.
PMH
o Stone in the kidney –treated by ESWL two
occasions
Case study
The phalanges are seen to
be asymmetrical with
subcortical bone
resorption on their radial
side. A minute examination
of the tufts will usually
reveal that the continuous
line of cortical bone which
delinates the tuft is
interrupted and the
appearance resembles a
lace border.
Sestamibi scanning
Sestamibi is a small protein which is
labeled with the radio-pharmaceutical
technetium-99. This very mild and safe
radioactive agent is injected into the
veins of a patient with parathyroid
disease and is absorbed by the
overactive parathyroid gland.
Minimally Invasive Radioguided
Parathyroid (MIRP) Surgery
Treatment of hypercalcaemia
Goals of treatment
o Stabilization and reduction of the calcium
level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Treatment of the underlying cause (when
possible)
Calcium balance
Calcium balance. On average, in a typical
adult approximately 1g of elemental
calcium (Ca+2) is ingested per day. Of this,
about 200mg/day will be absorbed and
800mg/day excreted.
Approximately 1kg of Ca+2 is stored in bone
and about 500mg/day is released by
resorption or deposited during bone
formation.
Of the 10g of Ca+2 filtered through the
kidney per day only about 200mg appears
in the urine, the remainder being
reabsorbed.
CALCIUM METABOLISM
Ca2+
1Kg
Ca2+
0.5gm/D
Ca2+ 1 gm/D
Ca2+
0.2gm/D
ECF Ca2+
Ca2+
9.8gm/D
URINE
Ca2+
10gm/D
Ca2+
0.2gm/D
Ca2+
0.8gm/D
ECF CALCIUM
EXTRACELLULAR
CALCIUM
PROTEIN
BOUND
50%
ACIDOSIS
IONIZED
FORM
45%
Responsible
for
Neuro-muscular
Stability
BOUND TO
OTHERS
5%
ALKALOSIS
Three types of cell produce and maintain bone.
• Osteoblasts (bone-forming cells) work at bone
surfaces where they secrete osteoid (unmineralised
collagen), modulate the crystallisation of
hydroxyapatite and influence the activity of
osteoclasts.
• Osteoclasts (bone-resorbing cells) are responsible
for the resorption (destruction) of old worn out
bone, which is necessary for the repair of bone
surfaces and the remodelling of bone.
• Osteocytes are osteoblasts which have become
embedded within the mineralised regions of bone.
They are involved in the sensing and translation of
information about the internal bone environment.
Bone turnover cycle
Stages of bone
fracture healing
FRACTURE
HEALING
PRIMARY
SECONDARY
Impaction stage
SURGICAL
RESORATION
OF ANATOMY
bone-resorbing cells on one side of
the fracture show a tunnelling
resorptive response, whereby they
re-establish new haversian systems
by providing pathways for the
penetration of blood vessels
Upto 7 days
Inflammation
stage
Upto 7 days
Two weeks
Primary soft
callus formation
stage
Callus mineralisation
stage
4 – 16 weeks
1 – 4 years
Remodelling
stage
CALCIUM HOMEOSTASIS
CAUSES OF HYPERCALCAEMIA
A. Endocrine Disorders Associated with
Hypercalcemia
1. Endocrine Disorders with Excess PTH Production
• Primary Sporadic hyperparathyroidism
• Primary Familial Hyperparathyroidism
• MEN I
• MEN IIA
• FHH and NSHPT
• Hyperparathyroidism - Jaw Tumor Syndrome
• Familial Isolated Hyperparathyroidism
2. Endocrine Disorders without Excess PTH
Production
• Hyperthyroidism
• Hypoadrenalism
• Jansen's Syndrome
CAUSES OF HYPERCALCAEMIA
Malignancy-Associated Hypercalcemia (MAH)
1. MAH with Elevated PTHrP
•
Humoral Hypercalcemia of Malignancy
•
Solid Tumors with Skeletal Metastases
•
Hematologic Malignancies
2. MAH with Elevation of Other Systemic Factors
•
MAH with Elevated 1,25(OH)2D3
•
MAH with Elevated Cytokines
•
Ectopic Hyperparathyroidism
•
Multiple Myeloma
C. Inflammatory Disorders Causing Hypercalcemia
1. Granulomatous Disorders
2. AIDS
D. Disorders of Unknown Etiology
1. Williams Syndrome
2. Idiopathic Infantile Hypercalcemia
B.
CAUSES OF HYPERCALCAEMIA
E.
1.
2.
3.
4.
5.
6.
7.
Medication-Induced
Thiazides
Lithium
Vitamin D
Vitamin A
Estrogens and Antiestrogens
Aluminium Intoxication
Milk-Alkali Syndrome
Drugs in hypercalcaemia
• Bisphosphonates -- Inhibit bone reabsorption eg.
Pamidronate,etidronate.
• Antineoplastic drugs -- Reduce bone turnover eg gallium
nitrate.
• Antihypercalcemic agents -- Inhibit bone resorption and
increase renal calcium excretion eg calcitonin.
• Glucocorticoids -- Inhibit cytokine release and have a
direct cytolytic effect on some tumor cells.
• Minerals -- Phosphate inhibits calcium absorption and
promotes calcium deposition.
• Calcimimetic agent -- Binds to and modulates the
parathyroid calcium-sensing receptor, increases
sensitivity to extracellular calcium, and reduces
parathyroid hormone secretion eg cinacalcet.
HYPERMAGNESAEMIA
CAUSE:• Renal failure
• Medications containing magnesium Ca2+ at
synapse
FEATURES:o Muscle weakness, Drowsiness
o Loss of tendon reflex
ACh at
neuromuscular
o ECG - PR wide QRS T
junction
o Depression of respiratory centre.
o Muscle
o Coma and Cardiac arrest
HYPERMAGNESAEMIA
TREATMENT:• Dialysis
• Calcium for cardiac arrhythmias.
• Inducing diuresis – Fluid load(4-5
litres of Saline) or Frusemide (2040mgm 8hrly)
• Adequate Calcium replacement.
HYPOMAGNESAEMIA
CAUSES:• Prolonged TPN
• GI losses – High output fistulae
• Alcoholism- Decreased tubular resorption
• Diuretics.
FEATURES:-
o
NM Excitability( transmitter release)
o Irregular tremors
o Irritability
o ECG-
ST, T inversion, QT (Hypokalaemia)
TREATMENT :- Magnesium Sulphate or Chloride ---30-50 mmols in 1 L of 5%Dextrose/24 hrs.
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
INTERPRETING BLOOD
GASES
• Look at the PaO2. Is the patient
hypoxaemic?
• What is the A-a gradient {Alveolar Arterial oxygen difference (A-a)DO2}
• (A-a)DO2 = FiO2 x (atmospheric pressure –
SVP of water) – PaCO2 – PaO2.
• (A-a)DO2=(FiO2 x{101-6.2}-PaCO2 -PaO2
APACHE
SCORE
RESULT
+4
>66.6
+3
46.766.5
+2
26.746.5
+1
0
<26.7
INTERPRETING BLOOD
GASES
• Look at the PaCO2.
• Look at the pH. Alkalotic or Acidic?
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
Respiratory acidosis
• Background: Respiratory acidosis is a
clinical disturbance that is due to alveolar
hypoventilation. Production of carbon
dioxide occurs rapidly, and failure of
ventilation promptly increases the partial
arterial pressure of carbon dioxide
(PaCO2). The reference range for PaCO2 is
36-44. Alveolar hypoventilation leads to an
increased PaCO2 (ie, hypercapnia). The
increase in PaCO2 in turn decreases the
HCO3-/PaCO2 and decreases pH.
What are the types of Respiratory Failure?
RESPIRATORY FAILURE
TYPE I FAILURE
HYPOXIC
PaO2 < 8kPa
NORMAL OR LOW
PaCO2
Impaired alveolar
function;
pneumonia,pulmonary
oedema; ARDS
TYPE II FAILURE
HYPERCAPNIC
PaO2 <8kPa
PaCO2 > 8kPa
Impaired alveolar
ventilation; COPD,
airway
impairment,chest wall
deformity,
neuromuscular
conditions
Compensation in
Respiratory acidosis
• In acute respiratory acidosis, compensation occurs
in 2 steps.
• The initial response is cellular buffering that
occurs over minutes to hours. Cellular buffering
elevates plasma bicarbonate (HCO3-) only slightly,
approximately 1 mEq/L for each 10-mm Hg increase
in PaCO2.
• In chronic respiratory acidosis, the second step is
renal compensation that occurs over 3-5 days. With
renal compensation, renal excretion of carbonic
acid is increased and bicarbonate reabsorption is
increased. In renal compensation, plasma
bicarbonate rises 3.5 mEq/L for each increase of
10 mm Hg in PaCO2.
Respiratory acidosis
The expected change in serum bicarbonate
concentration in respiratory acidosis can
be estimated as follows:
• Acute respiratory acidosis: HCO3increases 1 mEq/L for each 10-mm Hg rise
in PaCO2.
• Chronic respiratory acidosis: HCO3- rises
3.5 mEq/L for each 10-mm Hg rise in
PaCO2.
Respiratory alkalosis
• Respiratory alkalosis is a clinical disturbance
due to alveolar hyperventilation. Alveolar
hyperventilation leads to a decreased PaCO2
level (hypocapnia). In turn, the decrease in
PaCO2 level increases the ratio of
bicarbonate concentration (HCO3-) to PaCO2
and increases the pH level. Hypocapnia
develops when the lungs remove more carbon
dioxide than is produced in the tissues.
Respiratory alkalosis
Respiratory alkalosis can be acute or chronic.
• In acute respiratory alkalosis, the PaCO2
level is below the lower limit of normal and
the serum level is alkalemic.
• In chronic respiratory alkalosis, the PaCO2
level is below the lower limit of normal, but
the pH level is normal or near normal
because of renal compensation.
Respiratory alkalosis
• Acute hyperventilation with hypocapnia
causes a small early reduction in serum
bicarbonate due to cellular uptake of
bicarbonate. Acutely, plasma pH and
bicarbonate concentration vary
proportionately with the PaCO2 along a
range of 15-40 mm Hg.
• After a period of 2-6 hours, respiratory
alkalosis is compensated by the kidneys by
a decrease in bicarbonate reabsorption.
Respiratory alkalosis
• The expected change in serum bicarbonate
concentration ([HCO3-]) can be estimated as
follows:
• Acute - [HCO3-] falls 2 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
• Chronic - [HCO3-] falls 5 mEq/L for each
decrease of 10 mm Hg in the PaCO2 (Limit of
compensation: [HCO3-] = 12-20 mEq/L)
CONTROL OF VENTILATION
NEURAL CONTROL OF VENTILATION
VOLUNTARY
AUTOMATIC
CEREBRAL CORTEX
PONS &
MEDULLA
CORTICO-SPINAL TRACT
REGULATION OF VENTILATION
CHEMICAL CONTROL
1. CO2 - via
CSF H+ CONCENTRATION
2. O2 - via
CAROTID AND AORTIC BODIES
3. H+ - via
CAROTID AND AORTIC BODIES
NON CHEMICAL CONTROL
1. Afferents from Pons, Hypothalamus & Limbic System.
2. Afferent from Proprioceptors.
3. Afferents from pharynx, trachea & bronchi.
4. Vagal efferents from inflation/ deflation receptors in
lung.
5. Afferents from baroreceptors: arterial, atrial,
ventricular & pulmonary.
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
METABOLIC CHANGES
ACIDOSIS
EFFFECTS OF METABOLIC ACIDOSIS
o Increased respiratory drive (?){pH <7.1}.
o Decreased response to inotropes.
o H+ ions into cells and K+ out as buffering
action.
o Hyperkalaemia.
ANION GAP
• The formula
(Anion Gap = Na+ - HCO3- - Cl-).
• Also important to define the TYPE of
metabolic acidosis.
METABOLIC CHANGES
Anion Gap = Na+ - (HCO3- + Cl-)
CAUSES OF METABOLIC ACIDOSIS
Accumulation of H+
Loss of bicarbonate
Anion gap > 8 mmols/l Anion gap < 8mmols/l
Ketoacidosis
Vomiting /diarrhoea
Lactic acidosis
Small bowel fistula
ARF
Renal tubular acidosis
Salicylate poisoning
Calculating NaHCO3 = ½ x base deficit(mmols/l x weight(kg)
Very rarely needed!!!!!
3
COMPENSATORY MECHANISMS
1. BLOOD - Buffers.
2. RESPIRATORY – increased ventilation
– CO2 blown off.
3. KIDNEYS – HCO3 secreted all
reabsorbed.
BUFFERS IN BLOOD
• Plasma proteins.
• Imidazole groups of the histidine
residues of haemoglobin.
• Carbonic acid bicarbonate system.
• Phosphate system (intracellular)
Therefore use of bicarbonate only for the pH < 7.2 in an
inotrope resistant hypotensive patient
METABOLIC CHANGES
ALKALOSIS
EFFFECTS OF METABOLIC ALKALOSIS
o Reduced respiratory drive.
o H+ ions out of cells and K+ in as buffering
action.
o Hypokalaemia.
o Hypocalcaemia – tetany, paresthesia
COMPENSATORY MECHANISMS
1. RESPIRATORY – Reduced
respiration = retention of CO2 =
increased H+
2. RENAL – Increased HCO3 excretion
RELATION BETWEEN BASE
EXCESS AND pCO2
• Whenever the pH is normal, i.e., pH = 7.4.
then the PCO2 and the SBE are equal and
opposite. In such circumstances, if the PCO2
is described as a marked acidosis then
logically the SBE must be the exact opposite,
a marked alkalosis.
• Fortunately, the slope for BE/PCO2 when ph =
7.4 gives us this ratio: three units of change
in the SBE is equivalent to a five mmHg
change in the PCO2.
• Thus, (change in) pCO2: (change in) SBE = 5:3
• chpCO2/chSBE=5/3
INTERPRETING
BLOOD GASES
‘NORMAL’ BLOOD GASES
pH
DISTURBANCE OF ACID-BASE BALANCE
cPaCO2 = pH
PaCO2
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
cPaCO2 = pH
DOES NOT CORRESPOND
TO CHANGES
CORRESPONDS
TO CHANGES
HIGH IF
ACIDOTIC
SBE = pH
BASE DEFICIT
CORRESPONDS
TO CHANGES
LOW IF
ALKALOTIC
RESPIRATORY
ACIDOTIC =
BASE DEFICIT
ALKALOTIC =
BASE EXCESS
METABOLIC
DOES NOT
CORRESPOND TO CHANGES
SBE = pH
MIXED
INTERPRETATION OF BLOOD
GASES
‘NORMAL’ BLOOD GASES
pH
7.35 – 7.45
PaO2
13kPa
PaCO2
5.3kPa
HCO3
22 – 25mmol/l
Base deficit or
excess
-2 to +2 mmol/l
EXAMPLES
Example A:
• pH = 7.2,
• PCO2 = 60 mmHg,
• SBE = 0 mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is also
acid - therefore
contributing to the
acidosis.
SBE is normal - no
metabolic compensation.
Therefore, pure
respiratory acidosis.
Typical of acute
respiratory depression.
Magnitude: marked
respiratory acidosis
EXAMPLES
•
•
•
Example B:
•
• pH = 7.35,
• PCO2 = 60 mmHg,
• SBE = 7 mEq/L
•
•
Overall change is slightly acid.
Respiratory change is also acid therefore contributing to the
acidosis.
Metabolic change is alkaline therefore compensatory.
The respiratory acidosis is 20
mmHg on the acid side of normal
(40). To completely balance plus
20 would require 20 X 3 / 5 = 12
mEq/L SBE
The actual SBE is 7 eEq/L, which
is roughly half way between 0
and 12, i.e., a typical metabolic
compensation. The range is about
6mEq/L wide - in this example
between about 3 and 9 mEq/L.
Magnitude: marked respiratory
acidosis with moderate metabolic
compensation
EXAMPLES
•
•
Example C:
•
• pH = 7.15,
• PCO2 = 60 mmHg,
•
• SBE = -6 mEq/L
•
Overall change is acid.
Respiratory change is acid therefore contributing to the
acidosis.
Metabolic change is also acid therefore combined acidosis.
The components are pulling in
same direction - neither can
be compensating for the other
Magnitude: marked respiratory
acidosis and mild metabolic
acidosis
EXAMPLES
•
•
•
Example D:
• pH = 7.30,
• PCO2 = 30
mmHg,
• SBE = -10
mEq/L
•
•
•
•
Overall change is acid.
Respiratory change is alkaline therefore NOT contributing to the
acidosis.
Metabolic change is acid - therefore
responsible for the acidosis.
The components are pulling in opposite
directions. SBE is the acid component
so it is primarily a metabolic problem
with some respiratory compensation
The metabolic acidosis is 10 mEq/L on
the acid side of normal (0). To
completely balance 10 would require 10
* 5 / 3 = 17 mmHg respiratory alkalosis
(= 23 mmHg)
The actual PCO2 is 30 eEq/L which is
roughly half way between 23 and 40,
i.e., a typical respiratory compensation.
The range is about 10 mmHg wide - in
this example between about 27 and 37
mmHg.
Magnitude: marked metabolic acidosis
with mild respiratory compensation.
GOOD SURGERY
BUT
BAD
MANAGEMENT!!